Overall, these results displayed the key role of NRP1 in antitumor actions of lenvatinib in human HCC, where autophagy acts as a crucial mechanism involved in cell adaptation to lenvatinib treatment through NRP1 modulation, thus promoting cell resistance development, in which HIF-1α-associated hypoxia response seems to be a potential mediator. The gene discussed is NRP1; the disease is hepatocellular carcinoma.